Project 3: Functions of cell death selection in stochastic KRAS-driven mutagenesis in the lung

Coworkers: Silvia von Karstedt

Early cancer models have widely involved the use of carcinogens. Although these models have mostly been replaced by genetically-engineered approaches, carcinogen-induced models have recently regained attention. This was brought about by the fact that through vastly accelerated techniques of sequencing we now know that mutation rates in these carcinogen-induced cancers resemble those of human cancers much more closely. Interestingly, lung lesions induced by the carcinogen Urethane mostly present with Q61R oncogenic hotspot mutations in KRAS, suggesting strong selective pressure to be present in these tumours which favours this mutation over others. What this selective pressure might consist of has, however, remained unexplored. Therefore, this project investigates whether constitutive cell death induction is involved in Q61R selection. In this way, we aim to shed light on mechanisms which select for the most oncogenic variant within stochastic lung carcinogenesis. This project is funded through the Max-Eder Programme of the Deutsche Krebshilfe.